title: Impact of JC virus antibody testing in patients with Crohn's disease with loss of response to infliximab: a Markov model.
abstract: BACKGROUND
  The optimal treatment strategy for patients with Crohn's disease who have loss of response to the anti-tumor necrosis factor α medication infliximab is uncertain. Natalizumab has an alternative mechanism of action, but its use has been limited by the risk of progressive multifocal leukoencephalopathy. In this study, we performed a decision analysis assessing the impact of JC virus (JCV) antibody testing and natalizumab utilization for loss of response to infliximab.
  
  
  METHODS
  We constructed a Markov model to assess the difference between unscreened natalizumab use (option 1), JCV antibody testing with natalizumab when appropriate (option 2), and second anti-tumor necrosis factor α use (option 3). The base case was a 35-year-old man with severe Crohn's disease with loss of response to infliximab. The time horizon was 3 years. Results are reported in quality-adjusted life years (QALYs). Deterministic and probabilistic analyses were conducted. Markov analysis using a cohort of 5000 individuals was performed. The impact of JCV antibody status on outcomes in this model was assessed.
  
  
  RESULTS
  Option 2 was the preferred strategy (2.0880 QALYs), followed by option 1 (2.0875 QALYs) and option 3 (2.0808 QALYs). Patients in option 2 required fewer surgeries compared with option 3. Previous JCV infection was associated with reduced QALYs with all options that allowed for natalizumab use.
  
  
  CONCLUSIONS
  JCV antibody testing and subsequent treatment selection yield improved outcomes over natalizumab without testing or using only a second anti-tumor necrosis factor α in all patients.
authors.affiliation: *Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania; †Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; ‡Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and §Division of Gastroenterology and Nutrition, Department of Paediatrics, Anna Meyer Children's Hospital, University of Florence, Florence, Italy.
authors.forename: Frank I
authors.initials: FI
authors.lastname: Scott
authors.forename: Mark T
authors.initials: MT
authors.lastname: Osterman
authors.forename: Ryan A
authors.initials: RA
authors.lastname: McConnell
authors.forename: Monica
authors.initials: M
authors.lastname: Lorusso
authors.forename: Faten
authors.initials: F
authors.lastname: Aberra
authors.forename: Caroline
authors.initials: C
authors.lastname: Kerner
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lichtenstein
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000914:Antibodies, Viral / Q000097:blood*; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D007577:JC Virus / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008390:Markov Chains; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000069285:Infliximab